Resting-state networks representation of the global phenomena

Resting-state functional magnetic resonance imaging (rsfMRI) has been widely applied to investigate spontaneous neural activity, often based on its macroscopic organization that is termed resting-state networks (RSNs). Although the neurophysiological mechanisms underlying the RSN organization remain largely unknown, accumulating evidence points to a substantial contribution from the global signals to their structured synchronization. This study further explored the phenomenon by taking advantage of the inter- and intra-subject variations of the time delay and correlation coefficient of the signal timeseries in each region using the global mean signal as the reference signal. Consistent with the hypothesis based on the empirical and theoretical findings, the time lag and correlation, which have consistently been proven to represent local hemodynamic status, were shown to organize networks equivalent to RSNs. The results not only provide further evidence that the local hemodynamic status could be the direct source of the RSNs’ spatial patterns but also explain how the regional variations in the hemodynamics, combined with the changes in the global events’ power spectrum, lead to the observations. While the findings pose challenges to interpretations of rsfMRI studies, they further support the view that rsfMRI can offer detailed information related to global neurophysiological phenomena as well as local hemodynamics that would have great potential as biomarkers

Diminished Medial Prefrontal Activity behind Autistic Social Judgments of Incongruent Information

Individuals with autism spectrum disorders (ASD) tend to make inadequate social judgments, particularly when the nonverbal and verbal emotional expressions of other people are incongruent. Although previous behavioral studies have suggested that ASD individuals have difficulty in using nonverbal cues when presented with incongruent verbal-nonverbal information, the neural mechanisms underlying this symptom of ASD remain unclear. In the present functional magnetic resonance imaging study, we compared brain activity in 15 non-medicated adult males with high-functioning ASD to that of 17 age-, parental-background-, socioeconomic-, and intelligence-quotient-matched typically-developed (TD) male participants. Brain activity was measured while each participant made friend or foe judgments of realistic movies in which professional actors spoke with conflicting nonverbal facial expressions and voice prosody. We found that the ASD group made significantly less judgments primarily based on the nonverbal information than the TD group, and they exhibited significantly less brain activity in the right inferior frontal gyrus, bilateral anterior insula, anterior cingulate cortex/ventral medial prefrontal cortex (ACC/vmPFC), and dorsal medial prefrontal cortex (dmPFC) than the TD group. Among these five regions, the ACC/vmPFC and dmPFC were most involved in nonverbal-information-biased judgments in the TD group. Furthermore, the degree of decrease of the brain activity in these two brain regions predicted the severity of autistic communication deficits. The findings indicate that diminished activity in the ACC/vmPFC and dmPFC underlies the impaired abilities of individuals with ASD to use nonverbal content when making judgments regarding other people based on incongruent social information

Integrative Annotation of 21,037 Human Genes Validated by Full-Length cDNA Clones

The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology

Data_Sheet_1_Resting-state networks representation of the global phenomena.docx

Resting-state functional magnetic resonance imaging (rsfMRI) has been widely applied to investigate spontaneous neural activity, often based on its macroscopic organization that is termed resting-state networks (RSNs). Although the neurophysiological mechanisms underlying the RSN organization remain largely unknown, accumulating evidence points to a substantial contribution from the global signals to their structured synchronization. This study further explored the phenomenon by taking advantage of the inter- and intra-subject variations of the time delay and correlation coefficient of the signal timeseries in each region using the global mean signal as the reference signal. Consistent with the hypothesis based on the empirical and theoretical findings, the time lag and correlation, which have consistently been proven to represent local hemodynamic status, were shown to organize networks equivalent to RSNs. The results not only provide further evidence that the local hemodynamic status could be the direct source of the RSNs’ spatial patterns but also explain how the regional variations in the hemodynamics, combined with the changes in the global events’ power spectrum, lead to the observations. While the findings pose challenges to interpretations of rsfMRI studies, they further support the view that rsfMRI can offer detailed information related to global neurophysiological phenomena as well as local hemodynamics that would have great potential as biomarkers.</p

Neural basis for inferring false beliefs and social emotions in others among individuals with schizophrenia and those at ultra-high risk for psychosis.

Inferring beliefs and social emotions of others has different neural substrates and possibly different roles in the pathophysiology of different clinical phases of schizophrenia. The current study investigated the neural basis for inferring others\u27 beliefs and social emotions, as individual concepts, in 17 subjects at ultra-high risk for psychosis (UHR), 16 patients with schizophrenia and 20 healthy controls. Brain activity significantly differed from normal in both the left superior temporal sulcus (STS) and the inferior frontal gyrus (IFG) in the schizophrenia group while inferring others\u27 beliefs, whereas those of UHR group were in the middle of those in the schizophrenia and healthy-control groups. Brain activity during inferring others\u27 social emotions significantly differed in both the left STS and right IFG among individuals at UHR; however, there was no significant difference in the schizophrenia group. In contrast, brain activity differed in the left IFG of those in both the schizophrenia and UHR groups while inferring social emotion. Regarding the difference in direction of the abnormality, both the UHR and schizophrenia groups were characterized by hyper-STS and hypo-IFG activations when inferring others\u27 beliefs and emotions. These findings might reflect different aspects of the same pathophysiological process at different clinical phases of psychosis

Voxel-based analysis of the diffusion tensor

Introduction Diffusion tensor imaging (DTI) has provided important insights into the neurobiological basis for normal development and aging and various disease processes in the central nervous system. The aim of this article is to review the current protocols for DTI acquisition and preprocessing and statistical testing for a voxelwise analysis of DTI, focused on statistical parametric mapping (SPM) and tract-based spatial statistics (TBSS). Methods We tested the effects of distortion correction induced by gradient nonlinearity on fractional anisotropy (FA) maps or FA skeletons processed via two SPM-based methods (coregistration and FA template methods), or TBSS-based method, respectively. Results With two SPM-based methods, we found similar results in some points (e.g., significant FA elevation for uncorrected images in anterior-dominant white matter and for corrected images in bilateral middle cerebellar peduncles) and different results in other points (e.g., significantly larger FA for corrected images with coregistration method, but significantly smaller with FA template method in bilateral internal capsules, extending to corona radiata, and semioval centers). In contrast, there was no area with significant difference between uncorrected and corrected FA skeletons with TBSS-based method. Conclusion The discrepancy among these results was not explained in full, but possible explanations were misregistration and smoothing for the SPM-based methods and insensitivity to FA changes outside the local centers of white matter bundles for TBSS-based method